The use of cells, in particular, human cells, is now indispensable in disease research or new drug development. The demand therefor is expected to further increase in the future.
The cells are generally prepared by isolating them from tissues obtained from a biological organism, and are cultured to be used for various experiments and research. In such usage, differentiated cells are often used according to the target usage. However, the proliferation of differentiated cells ex vivo may be difficult. Moreover, differentiated cells have many problems, such as the rapid loss of original activity, considerable production cost, and great characteristic variation depending on the donor. For example, human hepatic cells are known for their variation in drug-metabolizing enzyme activity or drug-transporting activity. Further, hepatic cells obtained from biological tissue suffer a problematic rapid loss of function after culture.
To solve the above problems, in particular, the problem regarding cell proliferation ability, differentiated cells are often immortalized. For example, various methods for cell immortalization, including a method for introducing a SV (simian virus) 40 large T-antigen gene or a human telomerase gene into human hepatic cells, have been attempted (Non-patent Document 1). However, most immortalized cells lose their original differentiation character. There have been no reports of an immortalized cell fully exhibiting its original function. For example, telomerase genes are hardly expressed in normal cells of a human tissue. Further, using cancer genes for the production of immortalized cells is not regarded as desirable, considering the possibility of their deviation from the normal cells.
On the other hand, a method of isolating somatic stem cells having high proliferative ability from a biological tissue, and culturing and proliferating the cells ex vivo has been known as a means for obtaining a large number of normal primary cultured cells. Acquisition of somatic stem cells may be performed, for example, by a method for obtaining somatic cells from a biological tissue, and isolating somatic stem cells using a cell sorter according to the expression pattern of the cell-surface molecules. However, it is difficult to obtain a tissue containing desired somatic stem cells and select a suitable antibody for the somatic stem cells, and it is not easy to obtain a somatic stem cell population having high purity. Further, since the number of stem cells in a tissue is very small, a large number of cells (for example, 108 or more cells) is necessary as a starting material for the collection of a certain number of stem cells using a cell sorter. Moreover, even if a somatic stem cell population having high purity can be obtained, it is difficult to proliferate the cells by culture (in particular, it is difficult to culture the cells while maintaining the original properties of the somatic stem cells).
A method for proliferating pluripotent stem cells such as ES cells or iPS cells, and inducing differentiation of the proliferated cells to obtain the desired differentiated cells, has also been known. Although some reports confirmed differentiation of a part of ES cells or iPS cells, their differentiation efficiencies are insufficient at present, and various other cells are often contained. Thus the isolation of a highly pure differentiated cell population remains an arduous task.
Under such circumstances, there has been a strong need for a method for stably supplying a highly pure somatic stem cell population having a certain differentiation ability.